重组人骨形态发生蛋白2修饰的组织工程化骨修复眼眶骨折的实验研究

Experimental study of recombinant human bone morphogenetic protein 2 modified tissue engineered bone in reconstruction of orbital fracture

目的 探讨组织工程化骨修复眼眶骨折缺损的治疗效果.方法 体外构建以自体骨髓基质干细胞（BMSC）为种子细胞、可降解吸收的生物材料聚乳酸羟基乙酸聚合物（PLGA）为载体、重组人骨形态发生蛋白2（rhBMP-2）为生长因子的组织工程化骨,将实验动物分为对照组（植入PLGA/rhBMP-2复合物）和实验组（植入组织工程化骨）,观察术后1个月、3个月和6个月伤口愈合情况、并发症及眼眶外观、CT影像学和组织学变化.结果 术后所有动物伤口愈合良好,无并发症和眼球凹陷.CT三维成像显示术后3个月实验组的缺损范围[（25.1±6.8） mm2]小于对照组[（55.3±7.7）mm2]；术后6个月,实验组的眼眶骨折缺损消失,而对照组仍存在.组织学结果显示,术后1个月即可观察到实验组植入区边缘植入物开始缓慢吸收,少量成骨细胞沿支架长人材料内,而对照组未观察到；术后3个月可见实验组形成条带状新生骨长入将其分割包绕呈交叉排列,材料降解吸收明显高于对照组；术后6个月实验组植人材料完全被降解吸收,同时被新生骨组织取代,植入物与自身骨组织紧密结合,融为一体.而对照组仅部分降解吸收.结论 重组人骨形态发生蛋白2修饰的组织工程化骨具有较强的传导成骨和诱导成骨活性,生物相容性好,材料可完全降解,为骨组织取代,对眼眶骨折缺损具有较好的修复效果.

Objective To study the efficiency of tissue engineered bone modified by recombinant human bone morphogenetic protein 2 （rhBMP-2） in reconstruction of orbital fracture.Methods Tissue engineered bone was established in vitro by using antologous bone marrow stromal cells as daughter cells,degradable absorbable biomaterial PLGA as vector and rhBMP-2 as growth factor.The laboratory animals were divided into control group （implanted with PLGA/rhBMP-2） and experimental group （implanted with tissue engineered bone）.Wound healing,complications,orbit appearance,CT imaging and histological changes were observed at one,three and six months later after the surgery.Results All the animals were with well healed wounds.Neither complications nor enophthalmus was observed.The 3-D CT scan showed that orbital floor defect scope was smaller [ （25.1±6.8）mm2 vs （55.3±7.7）mm2] and CT values was higher in experiment group at 3 months later than in controls.Six months later after operation,the bone defect disappeared in experimental group but still existed in the controls.Marginal absorption of implanted bone with a small number of osteoblasts penetrating along the stent into the biomaterial was noted in the experimental group as early as one month later after operation,but not in the controls.At 3 months later,the experimental group showed strips of newly formed bone growing into or encapsulating the biomaterial,intersecting with each other and grew,with greater level of biomaterial degradation as compared with controls.At 6 months later,the implanted materials in experimental group were totally absorbed,replaced by newly formed osseous tissues,or fused perfectly with.inherent bone tissue.In contrast,the implants in controls showed only partial degradation and absorbance.Conclusions The tissue engineered bone modified by human bone morphogenetic protein 2 may well conduct and induce the activity of bone formation.Good biocompatibility and total degradability indicate that the implant is efficient in reconstruction of orbital fracture defects.